text: In the 1950s and 1960s, steroidogenic pathways that included cholesterol conversion to progesterone through a complex pathway involving multiple steps were identified, and, among them, a pathway for cortisol synthesis showing specific enzymatic steps that included hydroxylation reactions at position 21 (21-hydroxylation) mediated by cytochrome P450 enzymes. Cytochrome P450 enzymes were then described, and steroid 21-hydroxylation was associated with cytochrome P450.
  In the 1980s and 1990s, partial-length bovine Cyp21 cDNA clones were identified as related to human CYP21A2. Researchers discovered mutations in the CYP21A2 gene associated with congenital adrenal hyperplasia (CAH). 
  From the 1990s onward, specific mutations were correlated with different forms/severity levels of CAH. Genotype/phenotype correlations were investigated for improved diagnostic accuracy.